接受培格西他单抗治疗的阵发性睡眠性血红蛋白尿症成人患者，其疗效和安全性可维持长达3年。
Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan.
作者信息
de Castro Carlos, Kelly Richard J, Griffin Morag, Patriquin Christopher J, Mulherin Brian, Höchsmann Britta, Selvaratnam Veena, Wong Raymond Siu Ming, Hillmen Peter, Horneff Regina, Uchendu Uchendu O, Zhang Yiwei, Surova Elena, Szamosi Johan, de Latour Regis Peffault
机构信息
Duke Blood Cancer Center, Duke University, 2400 Pratt Steet, Durham, NC, 27705, USA.
Department of Haematology, St. James's University Hospital, Leeds, UK.
出版信息
Adv Ther. 2025 Sep;42(9):4641-4658. doi: 10.1007/s12325-025-03310-8. Epub 2025 Jul 28.
INTRODUCTION
Pegcetacoplan, the first C3 and C3b inhibitor for paroxysmal nocturnal hemoglobinuria (PNH), demonstrated efficacy and safety in C5 inhibitor-experienced and -naive patients in the phase 3 studies PEGASUS (NCT03500549) and PRINCE (NCT04085601), respectively. This integrated analysis of PEGASUS, PRINCE, and their subsequent open-label extension study (NCT03531255) evaluated pegcetacoplan long-term efficacy and safety.
METHODS
Efficacy was assessed from pegcetacoplan initiation through 2.5 years (PRINCE) and 3 years (PEGASUS) by measuring hemoglobin, lactate dehydrogenase (LDH), absolute reticulocyte count (ARC), indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores. Transfusion avoidance and safety were assessed during pegcetacoplan monotherapy. Of 133 patients in PRINCE and PEGASUS, 114 enrolled in the extension. Most patients (PRINCE, 81.1%; PEGASUS, 75.0%) were transfusion dependent at trial entry and baseline hemoglobin was below normal.
RESULTS
Pegcetacoplan markedly and rapidly (within 4 weeks) improved all efficacy measures, which stabilized close to (hemoglobin, FACIT-Fatigue) or within (LDH, ARC, indirect bilirubin) normal range for up to 3 years; annual transfusion avoidance rates were 79.5-86.4% in PRINCE and 71.2-79.2% in PEGASUS. No new safety concerns were identified over 3 years. Serious adverse events were reported in 73 (55.3%) patients, deemed pegcetacoplan related in 6 (4.5%) patients. Most injection site reactions were mild, and their incidence decreased over time. Five (3.8%) deaths occurred (none deemed pegcetacoplan related); 37 (28.0%) patients experienced clinically significant and laboratory-confirmed breakthrough hemolysis; 4 thrombotic events occurred in 3 (2.3%) patients; no meningitis cases were reported.
CONCLUSION
Pegcetacoplan efficacy and safety was sustained for up to 3 years in patients with PNH, with or without prior C5 inhibitor treatment, verifying the long-term favorable clinical profile of this proximal complement inhibitor.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03500549 (PEGASUS), NCT04085601 (PRINCE), and NCT03531255 (307 OLE).
引言
培格西他单抗是首个用于阵发性睡眠性血红蛋白尿（PNH）的C3和C3b抑制剂，在3期研究PEGASUS（NCT03500549）和PRINCE（NCT04085601）中，分别在有C5抑制剂使用经验和无该经验的患者中证明了其有效性和安全性。这项对PEGASUS、PRINCE及其后续开放标签扩展研究（NCT03531255）的综合分析评估了培格西他单抗的长期有效性和安全性。
方法
通过测量血红蛋白、乳酸脱氢酶（LDH）、绝对网织红细胞计数（ARC）、间接胆红素以及慢性病治疗功能评估（FACIT）-疲劳评分，评估从开始使用培格西他单抗起至2.5年（PRINCE研究）和3年（PEGASUS研究）期间的疗效。在培格西他单抗单药治疗期间评估避免输血情况和安全性。PRINCE和PEGASUS研究中的133例患者中，114例进入了扩展研究。大多数患者（PRINCE研究中为81.1%；PEGASUS研究中为75.0%）在试验入组时依赖输血，且基线血红蛋白低于正常水平。
结果
培格西他单抗显著且迅速（在4周内）改善了所有疗效指标，这些指标在长达3年的时间里稳定在接近（血红蛋白、FACIT-疲劳）或处于（LDH、ARC、间接胆红素）正常范围内；PRINCE研究中的年度避免输血率为79.5 - 86.4%，PEGASUS研究中为71.2 - 79.2%。3年内未发现新的安全问题。73例（55.3%）患者报告了严重不良事件，其中6例（4.5%）被认为与培格西他单抗相关。大多数注射部位反应为轻度，且其发生率随时间下降。发生了5例（3.8%）死亡（均不认为与培格西他单抗相关）；37例（28.0%）患者经历了临床显著且经实验室确认的突破性溶血；3例（2.3%）患者发生了4次血栓事件；未报告脑膜炎病例。
结论
在有或无先前C5抑制剂治疗的PNH患者中，培格西他单抗的有效性和安全性可维持长达3年，证实了这种近端补体抑制剂长期良好的临床特征。
试验注册
ClinicalTrials.gov NCT03500549（PEGASUS）、NCT04085601（PRINCE）和NCT03531255（307 OLE）
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